Since the isolation of the first substantial number of guaianolides in the 1950's interest in this class of hydroazulenic sesquiterpene lactones has continually increased. NMR, ORD, mass spectral, and X-ray studies have revealed the gross structure as well as the relative and absolute configuration of a variety of guaianolides. A pioneering conformational analysis has also been done. Biological screening of some guaianolides has shown that several of the more highly oxygenated compounds have significant effects on living organisms, such as cytotoxic and anti-tumor activities. Dehydrocostuslactone was most recently isolated in 1967 from a crude Asian drug used to treat stomach ailments. On the basis of limited chemical and spectroscopic evidence it was assigned a guaianolide structure. Neither its biological properties nor its detailed stereochemistry has been established. The objective of this project basically is two-fold: 1) to synthesize various alpha-methylene-alpha butyrolactones in the Costuslactone family from unnatural starting materials and thus to confirm the structure and to establish the complete stereochemistry of these Costuslactones and concurrently, 2) to generate experimental data concerning the general course and stereochemistry of reactions of variously substituted hydroazulene systems. The experience acquired in $ this work may make possible future planning and execution of total (possibly stereoselective) syntheses of more complex guaianolides whose effects on living cells have been well characterized. Broad biological screening of synthetic Costuslactones (and derivatives) have been arranged. The spectroscopic and chemical methods to be used are those of modern synthetic organic chemistry. The key synthetic steps involve 1) a pinacol rearrangement of a decalin glycol monotosylate to a keto hydroazulene, 2) attachment of an acetate side chain via enamine or enolate alkylation, 3) stereoselective carbonyl reduction giving a trans-hydroxyester, 4) Wittig methylenation of the ketone carbonyl of a keto lactone, and 5) alpha-methylenation of a alpha-butyrolactone. Extension of this synthetic scheme to guaianolide derivatives of potential biological interest (e.g. diepoxides) is discussed.